Tirzepatide for the Treatment of Cannabis Use Disorder

Tirzepatide for the Treatment of Cannabis Use Disorder: A Pilot Double-blind, Placebo-controlled, Crossover Trial

This is a pilot randomized cross-over trial to examine the effects of tirzepatide on cue-reactivity among individuals with cannabis use disorder.

Study Overview

• Status: Not yet recruiting
• Conditions: Cannabis Use Disorder
• Intervention / Treatment: Drug: Tirzepatide; Drug: Placebo

Detailed Description

This is a pilot randomized cross-over trial to examine the effects of tirzepatide on cue-reactivity among individuals with cannabis use disorder. Eligible participants will be scheduled in random order to receive either tirzepatide or placebo injection in double-blind fashion and cross-over design. Outcomes will be assessed at the following study visit. Washout period of at least 4 weeks will be required between tirzepatide or placebo injections. Primary outcome of interest is cue-induced craving to cannabis-related visual cues.

• Study Type: Interventional
• Enrollment (Estimated): 6
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Mary R Shen, MD; Phone Number: 6177325752; Email: mshen4@bwh.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• English speaking adults aged 18 and above
• Diagnosed with DSM-5 cannabis use disorder, severe

Exclusion Criteria:

• Active psychosis, active suicidality or homicidality or any psychiatric condition that impair ability to provide informed consent
• Any current or lifetime diagnosis of eating disorders including anorexia, bulimia, binge eating or
• Comorbid substance use disorder
• BMI<21 kg/m2
• Current or lifetime diagnosis of Type 1 or Type 2 diabetes
• Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2
• Use of any glucagon-like peptide -1 agonist medications in the prior 3 months
• Anticipating receipt of any glucagon-like peptide-1 agonist medications during the trial
• Current hypoglycemia as indicated by a blood sugar level of <71 mg/dL measured at baseline visit, as well as visits 2 and 4.
• Untreated cholelithiasis or gallbladder disease
• History of acute myocardial infarction, cerebrovascular accident (stroke), unstable angina, or congestive heart failure in the last 90 days
• Systolic blood pressure persistently above 160 mmHg or diastolic blood pressure persistently above 100 mmHg during screening
• History of inflammatory bowel disease, bariatric surgery, pancreatitis, diabetic gastroparesis, or non-arteritic anterior ischemic optic neuropathy
• Liver function test greater than 3 times upper normal limit
• Renal impairment as indicated by estimated glomerular filtration rate (eGFR) of <30
• History of hypersensitivity or allergy to tirzepatide
• Pregnant or breastfeeding
• Individuals taking glucagon-like peptide-1 agonists or other weight loss drugs.
• Anticipated to participate in a concurrent drug trial
• Any other reason or clinical condition that the investigators judge may interfere with study participation and/or be unsafe for a participant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: tirzepatide; 2.5mg subcutaneous injection once	Drug: Tirzepatide; 2.5mg subcutaneous injection once
Placebo Comparator: placebo; matching placebo subcutaneous injection once	Drug: Placebo; Saline placebo subcutaneous injection once

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cue-Induced Craving	Craving scores will be assessed using a cue-reactivity paradigm in which participants are exposed to cannabis]-related cues. Scores range from 0 to 30, with higher scores indicating greater craving intensity.	5 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serious adverse event	Incidence of serious adverse events	5 weeks
Abstinence	Percent days abstinent from cannabis	5 weeks
Weight	Weight	5 weeks
Blood sugar	Blood glucose	5 weeks
Hemoglobin A1c	Hemoglobin A1c	5 weeks
Cravings	Cannabis craving scale using the 12-item questionnaire, each item scored on a 1-7 sale. Higher scores (either average or summed) indicates stronger cravings.	5 weeks
Depression severity as measured by the Patient Health Questionnaire-8 (PHQ-8)	Depression severity as measured by the Patient Health Questionnaire-8 (PHQ-8). The PHQ-8 assesses depression severity over the past two weeks. Total scores range from 0 to 24, with higher scores indicating greater depression severity (worse outcome). Score interpretation: 0-4 (none), 5-9 (mild), 10-14 (moderate), 15-19 (moderately severe), 20-24 (severe depression).	5 weeks
Anxiety severity as measured by the Generalized Anxiety Disorder-7 scale (GAD-7)	The GAD-7 assesses anxiety symptom severity over the past two weeks. Total scores range from 0 to 21, with higher scores indicating greater anxiety severity (worse outcome). Score interpretation: 0-4 (minimal anxiety), 5-9 (mild), 10-14 (moderate), 15-21 (severe anxiety).	5 weeks
Suicidality as measured by the C-SSRS (Columbia-Suicide Severity Rating Scale)	The C-SSRS assesses the presence and severity of suicidal ideation and behavior. Suicidal ideation severity scores range from 0 to 5 (0=no ideation, 1=wish to be dead, 2=non-specific active suicidal thoughts, 3=active suicidal ideation with methods, 4=suicidal intent, 5=suicidal intent with plan), with higher scores indicating greater severity (worse outcome). The scale also captures suicidal behavior as binary yes/no responses.	5 weeks

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Investigators: Principal Investigator: Joji Suzuki, Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: November 25, 2025
• First Submitted That Met QC Criteria: November 25, 2025
• First Posted (Estimated): December 5, 2025

Study Record Updates

• Last Update Posted (Actual): December 18, 2025
• Last Update Submitted That Met QC Criteria: December 16, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: tirzepatide
• Additional Relevant MeSH Terms: Amino Acids, Peptides, and Proteins; Proteins; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide; Tirzepatide
• Other Study ID Numbers: 2025P002984

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No